Regulation of amyloid-beta clearance by the small GTPase Arf6 and the phospholipid kinase PIP5K

点击翻译按钮获取中文摘要

The plasma membrane receptors Megalin and LRP1, play a pivotal role in elimination of the Amyloid-beta peptide (Abeta), which is crucially involved in Alzheimer's disease, from the brain. In brain microvascular endothelial cells and choroid plexus epithelial cells, both receptors uptake Abeta from the brain fluid and transport them to the blood. In this research we find that the small GTPase Arf6 and the phospholipid kinase PIP5K bind to the cytoplasmic domains of Megalin and LRP1. We also demonstrate that knockdown of Arf6 causes accumulation of Megalin and LRP1 at intracellular endosomes and significant increase of the expression level of those proteins. These results indicate that Arf6 regulates transport of Megalin and LRP1 to lysosomes for degradation.